Affinage

COCH

Cochlin · UniProt O43405

Length
550 aa
Mass
59.5 kDa
Annotated
2026-06-09
90 papers in source corpus 22 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COCH encodes cochlin, a secreted extracellular matrix glycoprotein built from an N-terminal LCCL (FCH) domain and two collagen-binding type A (vWFA) domains, expressed at high levels in fibrocytes of the cochlear spiral limbus and ligament and the vestibular crista ampullaris (PMID:9441737, PMID:9806553, PMID:11709536). Cochlin is among the most abundant proteins of the inner ear (PMID:16481359), transits the ER/Golgi secretory pathway, is N-glycosylated, and is proteolytically cleaved between the LCCL and vWFA domains — a cleavage mediated by aggrecanase-1 (ADAMTS-4) during inflammation that releases the LCCL domain as a soluble fragment (PMID:12843317, PMID:26256111). Secreted cochlin self-assembles into extracellular deposits that co-localize with fibronectin and binds selectively to highly N-sulfated glycosaminoglycans such as heparin (PMID:12928864, PMID:35901072); loss of cochlin disrupts collagen fibril organization and tendon mechanical properties, underscoring a structural ECM role beyond the ear. Dominant missense mutations in the LCCL and vWFA domains cause DFNA9 sensorineural hearing loss and vestibular dysfunction through a dominant-negative/gain-of-function mechanism: the NMR-defined LCCL fold misfolds, mutant cochlin forms aberrant stable disulfide-bonded dimers and cytotoxic oligomers, and these mutants show impaired ECM integration, reduced aggrecanase cleavage, and diminished GAG binding (PMID:9806553, PMID:11574466, PMID:20228067, PMID:25230692, PMID:26256111, PMID:35901072); knockout mice retain normal early hearing, excluding haploinsufficiency, while G88E knock-in mice phenocopy the dominant disease (PMID:16078052, PMID:18697796, PMID:21073934). In contrast, biallelic truncating/loss-of-function variants cause recessive nonsyndromic hearing loss (DFNB110) through loss of cochlin protein (PMID:29449721, PMID:32939038). The cleaved LCCL domain additionally functions as an innate antibacterial effector at brain barrier tissues, and a distinct population of COCH-expressing CA3 hippocampal neurons drives social-stress-induced anxiety via MTF1-activated Cacna1h burst firing onto lateral septal GABAergic neurons (PMID:34965426).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 Medium

    Established cochlin as a candidate secreted ECM protein with collagen-binding vWFA domains and inner-ear-restricted expression, defining the molecular starting point.

    Evidence cDNA cloning, domain/sequence analysis, and tissue expression panel

    PMID:9441737

    Open questions at the time
    • No direct demonstration of secretion or matrix function
    • LCCL domain function not yet defined
  2. 1998 High

    Linked COCH missense mutations in the LCCL domain to dominant DFNA9 hearing loss and vestibular dysfunction, tying the gene to a defined Mendelian phenotype and to pathological ground-substance deposits.

    Evidence Mutation sequencing across kindreds and in situ hybridization of inner ear sections

    PMID:9806553

    Open questions at the time
    • Mechanism connecting mutation to deposits unresolved
    • Dominant vs loss-of-function basis unknown
  3. 2001 High

    Resolved the LCCL domain fold and showed most DFNA9 mutations destabilize it, providing structural rationale for pathogenicity.

    Evidence NMR structure with bacterial expression and folding assessment of mutant domains

    PMID:11574466

    Open questions at the time
    • Folding tested only for isolated bacterial domain, not full-length glycosylated protein
    • Binding partner blocked by W117R not identified
  4. 2001 High

    Localized cochlin protein and mRNA to the fibrocytes lost in DFNA9 temporal bones and detected processed isoforms, connecting expression to disease histopathology.

    Evidence In situ hybridization, immunohistochemistry, western blot of fetal cochlear extracts; 2D proteomics of bovine inner ear

    PMID:11278165 PMID:11709536

    Open questions at the time
    • Identity and origin of smaller isoforms not yet defined
    • Processing enzymes unknown
  5. 2003 High

    Defined cochlin's secretory route, N-glycosylation, and proteolytic separation of the LCCL from vWFA domains, and showed mutants are still secreted — shifting pathogenesis to the extracellular space.

    Evidence Transfection with secretion/glycosylation assays, immunocytochemistry, plus matrix deposition immunofluorescence

    PMID:12843317 PMID:12928864

    Open questions at the time
    • Protease responsible for cleavage not identified
    • Self-assembly vs partner-complex basis of deposition unresolved
  6. 2004 Medium

    Identified the perilymph-specific LCCL-containing CTP fragment, establishing that the mutation-bearing domain is liberated as a distinct circulating isoform.

    Evidence Isoform-specific antibody western blots of perilymph vs tissue in human and bovine samples

    PMID:14733925

    Open questions at the time
    • Functional role of CTP not addressed
    • Single-lab antibody-based detection
  7. 2005 High

    Genetic knockout established that DFNA9 is not haploinsufficiency, pointing to a dominant-negative/gain-of-function disease mechanism.

    Evidence Coch knockout mouse with ABR phenotyping and LacZ reporter expression mapping

    PMID:16078052

    Open questions at the time
    • Molecular nature of dominant-negative effect not shown
    • Late-onset null phenotype not yet characterized
  8. 2006 High

    Confirmed cochlin as the principal protein of the DFNA9 inner ear deposits and demonstrated its extracellular stability, linking aggregation to disease morphology.

    Evidence Proteomics and immunohistochemistry on temporal bones with knockout comparison

    PMID:16481359

    Open questions at the time
    • Biochemical trigger of in vivo aggregation not defined
  9. 2008 High

    A G88E knock-in showed dominant heterozygous progressive vestibular-then-auditory decline, modeling DFNA9 and confirming the dominant-negative mechanism in vivo.

    Evidence Knock-in mouse with VsEP, ABR, DPOAE across ages

    PMID:18697796

    Open questions at the time
    • Molecular basis of vestibular-before-cochlear sequence unexplained
  10. 2010 Medium

    Demonstrated the biochemical mechanism of dominant negativity: mutant cochlin forms stable disulfide dimers, recruits wild-type protein into reducing-resistant cytotoxic oligomers, and is toxic in vivo.

    Evidence Non-reducing/reducing western blots, cytotoxicity assays in vitro and in vivo; combined with paired knockout/knock-in ABR-VsEP epistasis

    PMID:20228067 PMID:21073934

    Open questions at the time
    • Aggregation pathway and cytotoxic species not structurally defined
    • Single-lab biochemistry
  11. 2012 Medium

    Showed vWFA2-domain mutations (F527C) can drive aberrant disulfide-bonded complexes retained in the ER/Golgi while sparing collagen binding, extending pathogenic mechanisms beyond the LCCL domain.

    Evidence Transfection, reducing/non-reducing western blot, recombinant vWFA2 biochemistry

    PMID:22610276

    Open questions at the time
    • In vivo consequences of ER retention not tested
    • Single-lab
  12. 2014 High

    Resolved two mechanistic classes of DFNA9 mutation — vWFA aggregation/ER-block vs LCCL intracellular dimers — both abolishing secretion, and correlated them with genotype-phenotype and onset.

    Evidence Secretory-pathway tracking across eight mutations with clinical correlation

    PMID:25230692

    Open questions at the time
    • Why domain location dictates vestibular vs auditory bias not mechanistically explained
  13. 2015 Medium

    Identified aggrecanase-1 (ADAMTS-4) as the protease that cleaves cochlin and releases the LCCL domain during inflammation, and showed DFNA9 mutations impair this cleavage.

    Evidence In vitro aggrecanase cleavage assays on wild-type and mutant cochlins

    PMID:26256111

    Open questions at the time
    • In vivo relevance of impaired cleavage to deposits not demonstrated
    • Single-lab
  14. 2018 Medium

    Established a distinct recessive disease mechanism: biallelic truncating COCH variants cause prelingual deafness via loss-of-function, separating DFNB110 from dominant DFNA9.

    Evidence Sequencing and family co-segregation with audiovestibular phenotyping

    PMID:29449721

    Open questions at the time
    • Protein-level confirmation absent in this report
  15. 2020 Medium

    Extended and validated the recessive loss-of-function mechanism, showing splicing-disrupting and frameshift variants yield null alleles and loss of cochlin protein.

    Evidence Minigene splicing assays and COS7 expression/western blot

    PMID:32562050 PMID:32939038

    Open questions at the time
    • No tissue-level confirmation of protein loss in patients
    • Single-lab assays
  16. 2022 Medium

    Identified cochlin's selective N-sulfation-dependent binding to heparin/highly sulfated GAGs and showed all DFNA9 mutations diminish this binding, defining a matrix-anchoring activity disrupted in disease.

    Evidence Reporter-cell GAG binding assays with desulfation controls, cochlin/Fc cochlear immunostaining, GAG composition analysis

    PMID:35901072

    Open questions at the time
    • Which domain mediates GAG binding not localized
    • Physiological consequence of disrupted binding not tested in vivo
  17. 2021 Medium

    Revealed an unexpected neuronal role: COCH marks a CA3 hippocampal population that uses MTF1-driven Cacna1h burst firing onto lateral septal GABAergic neurons to mediate social-stress anxiety.

    Evidence Genetic targeting, transcriptomics, electrophysiology, circuit tracing, behavior in mice

    PMID:34965426

    Open questions at the time
    • Whether secreted cochlin protein contributes to this circuit, vs COCH as a marker, is unclear
    • Single-lab
  18. 2024 Medium

    Showed cochlin is required for tendon collagen fibril organization and mechanics, generalizing its structural ECM role beyond the inner ear.

    Evidence Cochlin knockout mouse with fibril imaging, biomechanics, and proteomics (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Molecular interactions in tendon matrix not defined
  19. 2025 Medium

    Assigned an innate-immune effector function to the cleaved LCCL domain at brain barrier tissues, with loss-of-function and domain-rescue establishing it as the antibacterial moiety.

    Evidence Transcriptomics, in situ hybridization, recombinant cochlin/LCCL delivery and mutant rescue in zebrafish (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Mechanism of bacterial clearance unknown
    • Mammalian relevance not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How cochlin's normal matrix-organizing, GAG-binding, and antibacterial functions integrate, and the structural identity of the cytotoxic mutant aggregate species in DFNA9, remain unresolved.
  • No structure of the full-length protein or its oligomeric deposits
  • Endogenous binding partner blocked by W117R never identified
  • Relationship between ear ECM role and neuronal/immune roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 1 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 3 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-168256 Immune System 1
Partners
ADAMTS4CACNA1HFN1MTF1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 COCH (Coch-5B2) encodes a secreted protein with a predicted signal peptide and two regions of extensive homology to the collagen-binding type A (vWFA) domains of von Willebrand factor, indicating a structural role in the extracellular matrix. High-level expression is restricted to human fetal inner ear (cochlea and vestibule). cDNA cloning, sequence analysis, tissue expression panel by Northern blot/RT-PCR, FISH mapping Genomics Medium 9441737
1998 Missense mutations in COCH (in the FCH/LCCL domain containing four conserved cysteines) cause autosomal dominant sensorineural hearing loss and vestibular dysfunction (DFNA9). COCH mRNA is expressed at high levels in fibrocytes of cochlear and vestibular neural regions, corresponding to areas showing histopathological acidophilic ground substance deposits in DFNA9 patients. Mutation analysis (sequencing), in situ hybridization of human and chicken inner ear sections Nature genetics High 9806553
2001 COCH mRNA and protein (cochlin) are expressed predominantly in fibrocytes of the spiral limbus and spiral ligament of the cochlea, and in fibrocytes of the connective tissue stroma of the crista ampullaris. These are exactly the cell types absent or markedly reduced in DFNA9 temporal bone sections, which show replacement by eosinophilic acellular material. Western blots of human fetal cochlear extracts show full-length cochlin and a smaller isoform. Immunohistochemistry with anti-cochlin antibody (raised against the N-terminal 135 aa FCH domain) confirms this localization. In situ hybridization, immunohistochemistry, western blot of human fetal cochlear extracts Human molecular genetics High 11709536
2001 The NMR structure of the LCCL domain of human cochlin (Coch-5b2) reveals a novel fold stabilized by disulfide bonds. Four of five known DFNA9 mutations (except Trp91Arg/W117R in human numbering) cause misfolding of the expressed domain when produced in bacteria, while the W117R mutant folds correctly but likely disrupts interaction with a binding partner, since it involves a solvent-exposed residue. NMR structure determination, bacterial expression of LCCL domain mutants, protein folding assessment The EMBO journal High 11574466
2001 Cochlin constitutes ~70% of bovine inner ear proteins and exists as multiple isoforms (at least 16 protein spots by 2D gel electrophoresis), showing charge and size heterogeneity indicative of post-translational processing at both transcriptional and post-translational levels. 2D gel electrophoresis, proteomic analysis of bovine inner ear Biochimica et biophysica acta Medium 11278165
2003 Cochlin is a secreted protein that passes through the endoplasmic reticulum and Golgi apparatus. It undergoes proteolytic cleavage between the FCH/LCCL domain and the vWFA domains, generating a ~50 kDa isoform lacking the entire LCCL domain (the mutation-bearing region). Cochlin is N-glycosylated in its mature secreted form. DFNA9 mutant cochlins are not retained intracellularly and are secreted adequately through the Golgi/ER pathway, also undergoing proteolytic cleavage and glycosylation, suggesting pathogenesis occurs after secretion in the extracellular matrix. Transient transfection of mammalian cell lines, western blot of lysates and media, immunocytochemistry, glycosylation assay Journal of medical genetics High 12843317
2003 Wild-type cochlin accumulates in extracellular deposits that co-localize with fibronectin matrix, while DFNA9 LCCL-domain mutant cochlins show altered or absent extracellular matrix deposition patterns despite normal synthesis and secretion, suggesting DFNA9 pathology results from failure of cochlin to integrate correctly into the extracellular matrix, either by impaired self-assembly or failure to form appropriate complexes with other matrix components. Transient transfection, western blot, immunofluorescence of extracellular deposits in cell culture Human genetics Medium 12928864
2004 A novel short cochlin isoform (~16 kDa in human, 18-23 kDa in cow), termed Cochlin-tomoprotein (CTP), is detected specifically in perilymph but not in inner ear tissue. CTP corresponds to the N-terminus of full-length cochlin and contains the LCCL domain with all known DFNA9 mutation sites. Isoform-specific anti-cochlin antibodies, western blot of perilymph and inner ear tissue from human and bovine samples Biochemical and biophysical research communications Medium 14733925
2005 A COCH mutation (C542F) in the vWFA2 domain alters an evolutionarily conserved cysteine residue and disrupts intramolecular disulfide bond formation in cochlin, as shown by western blot under non-reducing versus reducing conditions. The C542F mutant cochlin is translated and secreted by transfected mammalian cells. Mammalian cell transfection, western blot under non-reducing and reducing conditions American journal of medical genetics. Part A Medium 16261627
2005 Targeted disruption (knockout) of mouse Coch downstream of the LCCL domain results in no detectable cochlin in the inner ear. Homozygous Coch-/- mice have normal auditory brainstem responses, demonstrating that DFNA9 is not caused by haploinsufficiency but likely by a dominant-negative or gain-of-function mechanism of mutant cochlin. A Coch-LacZ reporter allele detected Coch mRNA expression in nonsensory epithelial and stromal regions of the cochlea and vestibular labyrinth. Targeted gene disruption (knockout mouse), auditory brainstem response (ABR), LacZ reporter Human genetics High 16078052
2006 Cochlin is the most abundant protein in mouse and human cochleae by proteomic analysis. Immunohistochemistry of DFNA9 temporal bone sections shows cochlin staining of the characteristic cochlear and vestibular deposits (eosinophilic acellular material), indicating cochlin aggregation in the same inner ear structures where it is normally expressed. High-level cochlin expression and protein stability persist even after severe atrophy of the fibrocytes that normally express COCH, demonstrating the stability of secreted cochlin in the extracellular matrix. Immunohistochemistry on DFNA9 temporal bone sections, proteomic analysis of mouse and human cochleae, comparison with Coch null (-/-) knockout mice Human molecular genetics High 16481359
2008 A G88E knock-in mouse model (Coch^G88E/G88E) develops progressive vestibular dysfunction (elevated VsEP thresholds) detectable as early as 11 months of age, followed by progressive hearing loss (elevated ABR thresholds) at 21 months, establishing that cochlin dysfunction causes age-related progressive vestibular and auditory deficits. Heterozygous Coch^G88E/+ mice also develop elevated ABR thresholds similar to homozygotes, consistent with dominant-negative mechanism. Gene targeting (knock-in mouse), VsEP, ABR, distortion product otoacoustic emissions Human molecular genetics High 18697796
2010 Mutant cochlin (from DFNA9 mutations) forms a stable disulfide-bonded dimer, while wild-type cochlin forms dimers only transiently. The presence of mutant cochlin stabilizes wild-type cochlin in dimer conformation and eventually induces wild-type cochlin to form stable oligomers resistant to reducing agent. Mutant cochlin is cytotoxic both in vitro and in vivo. Western blot under reducing/non-reducing conditions, cell viability assays, in vivo cytotoxicity assay The Journal of biological chemistry Medium 20228067
2010 Coch(-/-) null mice show elevated VsEP thresholds at 13 and 21 months of age, and elevated ABR thresholds at 21 months (with absent ABRs in 9 of 11 mice). Coch(-/+) heterozygous mice do not show hearing deficits, whereas Coch(G88E/+) heterozygotes show elevated ABR thresholds similar to homozygotes, confirming that DFNA9 dominant inheritance is not due to haploinsufficiency but to a dominant-negative or gain-of-function effect. Vestibular function is compromised before cochlear function in both mouse models. ABR, VsEP in Coch-/- and Coch^G88E/G88E mouse models at multiple ages Hearing research High 21073934
2012 A novel COCH mutation p.F527C in the vWFA2 domain causes cochlin to form covalent disulfide-bonded complexes retained in the endoplasmic reticulum/Golgi complex. Biochemical analysis of the recombinant vWFA2 domain carrying p.F527C shows increased propensity for disulfide-bonded dimerization and reduced structural stability, but unaffected collagen-binding affinity of the vWFA2 domain. Mammalian cell transfection, immunocytochemistry, western blot under reducing/non-reducing conditions, in vitro biochemical analysis of recombinant vWFA2 domain Journal of molecular medicine (Berlin, Germany) Medium 22610276
2014 Functional analysis of eight COCH mutations reveals two distinct pathogenic mechanisms: (1) Two vWFA domain mutants are not transported from ER to Golgi and form high-molecular-weight aggregates in cell lysates; (2) Three LCCL domain mutants are detected as intracellular dimeric cochlins. Both classes result in abolishment of cochlin secretion. Genotype-phenotype analysis shows: LCCL domain mutations associate with accompanying vestibular dysfunction while vWFA domain mutations cause predominantly hearing loss; mutant cochlins that fail to be secreted correlate with earlier age of onset. Immunocytochemistry, western blot, tracking through secretory pathway in mammalian cell lines; comprehensive genotype-phenotype correlation Human mutation High 25230692
2015 Cochlin is cleaved by aggrecanase-1 (ADAMTS-4) during inflammation, releasing the LCCL domain as a secreted fragment. DFNA9-linked mutations in cochlin (P51S, V66G, G88E, I109T, W117R, V123E, C162Y) all demonstrate significantly reduced susceptibility to aggrecanase cleavage (novel V123E mutant shows ~20.5% of wild-type cleavage efficiency), suggesting that impaired post-translational LCCL domain cleavage may contribute to DFNA9 pathogenesis. In vitro aggrecanase cleavage assay on wild-type and mutant cochlins expressed in mammalian cells Human mutation Medium 26256111
2018 Homozygous nonsense variants in COCH (c.292C>T, p.Arg98*) cause autosomal recessive prelingual deafness with early-onset vestibular dysfunction. Heterozygous carriers have normal hearing, establishing that biallelic loss-of-function of COCH is sufficient to cause hearing loss via a recessive mechanism distinct from the dominant-negative mechanism of DFNA9 missense mutations. Genetic analysis (sequencing), family co-segregation study, audiological and vestibular phenotyping European journal of human genetics : EJHG Medium 29449721
2020 Novel COCH loss-of-function variants (two nonsense, one missense, one in-frame deletion) cause autosomal recessive nonsyndromic hearing loss. Minigene splicing assays demonstrate that the missense and in-frame deletion variants alter RNA splicing by creating an exon splicing silencer and abolishing an exon splicing enhancer, respectively, leading to frameshifts and predicted null alleles. Targeted gene panels, exome sequencing, minigene splicing assay Human genetics Medium 32562050
2020 A homozygous frameshift COCH variant in a human family results in major decrease in cochlin translation and loss-of-function, as demonstrated using COS7 cell lines, providing the first direct evidence of DFNB110 (recessive) cochlin loss-of-function at the protein level. COS7 cell line expression studies, western blot analysis of cochlin translation European journal of human genetics : EJHG Medium 32939038
2022 Cochlin binds selectively to highly sulfated glycosaminoglycans (GAGs), specifically heparin, via N-sulfation-dependent interaction (N-desulfation abolishes binding; 2-O- and 6-O-desulfation do not). All DFNA9 point mutations diminish cochlin binding to GAGs. Mouse cochlea contains moderately sulfated GAGs that cochlin (as cochlin/Fc fusion) binds, suggesting cochlin-GAG interaction is relevant to cochlear extracellular matrix function. Cochlin reporter cell β-galactosidase assay, GAG binding assay with desulfation controls, immunostaining of mouse cochlea with cochlin/Fc fusion protein, GAG composition analysis PloS one Medium 35901072
2021 COCH-expressing neurons in the distal ventral CA3 hippocampus co-express Mtf1 and Cacna1h. MTF1 activates Cacna1h transcription in these neurons, enabling burst action potentials. COCH neurons synapse directly with GABAergic inhibitory neurons in the lateral septum and mediate social-stress-induced anxiety-like behavior. Genetic targeting of COCH-expressing neurons, transcriptome analysis, electrophysiology, circuit tracing, behavioral assays Cell reports Medium 34965426
2024 Loss of Cochlin (Cochlin-/- mice) causes progressive alterations in collagen fibril organization in flexor tendons by 3 months of age and significant declines in tendon structural and material mechanical properties by 6 months. The Cochlin-/- tendon proteome shows consistent decreases in proteins associated with RNA metabolism, extracellular matrix production, and cytoskeleton, establishing Cochlin as a critical extracellular matrix protein for tendon homeostasis. Cochlin-/- knockout mouse model, collagen fibril imaging, biomechanical testing, quantitative proteomics bioRxivpreprint Medium
2025 Cochlin, expressed in brain barrier tissues including the pineal gland, area postrema, choroid plexus and meninges of zebrafish, mice and humans, contributes to brain defense against bacterial infection. Cochlin expression transiently increases upon Mycobacterium marinum infection in zebrafish larvae; delivery of recombinant cochlin reduces bacterial load; cochlin mutation inhibits bacterial clearance from the brain; and supplying the LCCL domain reverses this deficit, establishing the cleaved LCCL domain as the active antibacterial moiety. Transcriptome analysis, in situ hybridization, recombinant cochlin delivery, cochlin mutant zebrafish, LCCL domain rescue experiment bioRxivpreprint Medium

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nature genetics 270 9806553
1999 High prevalence of symptoms of Menière's disease in three families with a mutation in the COCH gene. Human molecular genetics 124 10400989
1997 Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9. Genomics 116 9441737
1999 A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects. Human molecular genetics 112 9931344
2006 Cochlin immunostaining of inner ear pathologic deposits and proteomic analysis in DFNA9 deafness and vestibular dysfunction. Human molecular genetics 102 16481359
2001 Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9. Human molecular genetics 89 11709536
2001 Identification of the protein product of the Coch gene (hereditary deafness gene) as the major component of bovine inner ear protein. Biochimica et biophysica acta 86 11278165
2003 Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease. European journal of human genetics : EJHG 75 14512963
2003 Subcellular localisation, secretion, and post-translational processing of normal cochlin, and of mutants causing the sensorineural deafness and vestibular disorder, DFNA9. Journal of medical genetics 70 12843317
2001 NMR structure of the LCCL domain and implications for DFNA9 deafness disorder. The EMBO journal 59 11574466
2000 DFNA9 is a progressive audiovestibular dysfunction with a microfibrillar deposit in the inner ear. The Laryngoscope 59 10942145
2014 Identification of pathogenic mechanisms of COCH mutations, abolished cochlin secretion, and intracellular aggregate formation: genotype-phenotype correlations in DFNA9 deafness and vestibular disorder. Human mutation 50 25230692
2005 A novel DFNA9 mutation in the vWFA2 domain of COCH alters a conserved cysteine residue and intrachain disulfide bond formation resulting in progressive hearing loss and site-specific vestibular and central oculomotor dysfunction. American journal of medical genetics. Part A 50 16261627
2001 Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families. Human mutation 49 11295836
1999 Progressive cochleovestibular impairment caused by a point mutation in the COCH gene at DFNA9. The Laryngoscope 45 10499067
2003 Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin. Human genetics 43 12928864
2008 A targeted Coch missense mutation: a knock-in mouse model for DFNA9 late-onset hearing loss and vestibular dysfunction. Human molecular genetics 42 18697796
2005 Vestibular deterioration precedes hearing deterioration in the P51S COCH mutation (DFNA9): an analysis in 74 mutation carriers. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 40 16151338
2010 Role of protein misfolding in DFNA9 hearing loss. The Journal of biological chemistry 38 20228067
2004 Identification of a novel Cochlin isoform in the perilymph: insights to Cochlin function and the pathogenesis of DFNA9. Biochemical and biophysical research communications 38 14733925
2010 Hearing and vestibular deficits in the Coch(-/-) null mouse model: comparison to the Coch(G88E/G88E) mouse and to DFNA9 hearing and balance disorder. Hearing research 37 21073934
2005 Audiometric, vestibular, and genetic aspects of a DFNA9 family with a G88E COCH mutation. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 37 16151339
2001 Hereditary otovestibular dysfunction and Ménière's disease in a large Belgian family is caused by a missense mutation in the COCH gene. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 37 11698812
2001 Speech recognition scores related to age and degree of hearing impairment in DFNA2/KCNQ4 and DFNA9/COCH. Archives of otolaryngology--head & neck surgery 34 11556850
2004 Absence of COCH mutations in patients with Meniere disease. European journal of human genetics : EJHG 31 14704763
2005 Targeted disruption of mouse Coch provides functional evidence that DFNA9 hearing loss is not a COCH haploinsufficiency disorder. Human genetics 29 16078052
2018 Lotus japonicus NOOT-BOP-COCH-LIKE1 is essential for nodule, nectary, leaf and flower development. The Plant journal : for cell and molecular biology 28 29570881
2020 On the pathophysiology of DFNA9: Effect of pathogenic variants in the COCH gene on inner ear functioning in human and transgenic mice. Hearing research 26 33421658
2003 Progressive late-onset sensorineural hearing loss and vestibular impairment with vertigo (DFNA9/COCH): longitudinal analyses in a belgian family. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 26 14501450
2012 Whole exome sequencing identifies a novel DFNA9 mutation, C162Y. Clinical genetics 25 22931125
2007 Phenotype description of a novel DFNA9/COCH mutation, I109T. The Annals of otology, rhinology, and laryngology 25 17561763
2015 Novel COCH p.V123E Mutation, Causative of DFNA9 Sensorineural Hearing Loss and Vestibular Disorder, Shows Impaired Cochlin Post-Translational Cleavage and Secretion. Human mutation 24 26256111
2013 Novel COCH mutation in a family with autosomal dominant late onset sensorineural hearing impairment and tinnitus. American journal of otolaryngology 24 23374487
2012 A novel COCH mutation associated with autosomal dominant nonsyndromic hearing loss disrupts the structural stability of the vWFA2 domain. Journal of molecular medicine (Berlin, Germany) 22 22610276
2019 A systematic review of hearing and vestibular function in carriers of the Pro51Ser mutation in the COCH gene. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 21 30806805
2018 Bi-allelic inactivating variants in the COCH gene cause autosomal recessive prelingual hearing impairment. European journal of human genetics : EJHG 21 29449721
2016 Histopathology of the Human Inner Ear in the p.L114P COCH Mutation (DFNA9). Audiology & neuro-otology 21 27023102
2015 Detailed hearing and vestibular profiles in the patients with COCH mutations. The Annals of otology, rhinology, and laryngology 21 25780252
2015 The legume NOOT-BOP-COCH-LIKE genes are conserved regulators of abscission, a major agronomical trait in cultivated crops. The New phytologist 21 26390061
2003 Cross-sectional analysis of hearing threshold in relation to age in a large family with cochleovestibular impairment thoroughly genotyped for DFNA9/COCH. The Annals of otology, rhinology, and laryngology 21 12656423
2021 A circuit of COCH neurons encodes social-stress-induced anxiety via MTF1 activation of Cacna1h. Cell reports 20 34965426
2016 Distinct vestibular phenotypes in DFNA9 families with COCH variants. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 20 26758463
2001 Hereditary cochleovestibular dysfunction due to a COCH gene mutation (DFNA9): a follow-up study of a family. Clinical otolaryngology and allied sciences 20 11843927
2014 Focal sclerosis of semicircular canals with severe DFNA9 hearing impairment caused by a P51S COCH-mutation: is there a link? Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 19 24662630
2000 Familial progressive vestibulocochlear dysfunction caused by a COCH mutation (DFNA9). Archives of neurology 19 10891988
2010 A novel mutation in COCH-implications for genotype-phenotype correlations in DFNA9 hearing loss. The Laryngoscope 18 21046548
2004 A novel locus for autosomal dominant non-syndromic hearing loss, DFNA31, maps to chromosome 6p21.3. Journal of medical genetics 18 14729819
2006 Clinical characteristics of a Dutch DFNA9 family with a novel COCH mutation, G87W. Audiology & neuro-otology 17 17264471
2020 Novel loss-of-function mutations in COCH cause autosomal recessive nonsyndromic hearing loss. Human genetics 15 32562050
2013 Clinical characterization of a novel COCH mutation G87V in a Chinese DFNA9 family. International journal of pediatric otorhinolaryngology 15 23993205
1999 The COCH gene: a frequent cause of hearing impairment and vestibular dysfunction? British journal of audiology 15 10890144
2022 AudioGene: refining the natural history of KCNQ4, GSDME, WFS1, and COCH-associated hearing loss. Human genetics 13 35038006
2019 Novel Mutations in KCNQ4, LHFPL5 and COCH Genes in Iranian Families with Hearing Impairment. Archives of Iranian medicine 12 31126177
2021 AON-based degradation of c.151C>T mutant COCH transcripts associated with dominantly inherited hearing impairment DFNA9. Molecular therapy. Nucleic acids 11 33815940
2021 Genotype-phenotype Correlation Study in a Large Series of Patients Carrying the p.Pro51Ser (p.P51S) Variant in COCH (DFNA9): Part I-A Cross-sectional Study of Hearing Function in 111 Carriers. Ear and hearing 11 34369416
2017 Identification of a rare COCH mutation by whole-exome sequencing : Implications for personalized therapeutic rehabilitation in an Austrian family with non-syndromic autosomal dominant late-onset hearing loss. Wiener klinische Wochenschrift 11 28733840
2022 Genotype-Phenotype Correlations of Pathogenic COCH Variants in DFNA9: A HuGE Systematic Review and Audiometric Meta-Analysis. Biomolecules 10 35204720
2022 Accelerated Cognitive Decline Associated With Hearing Loss and Bilateral Vestibulopathy: Insights From a Prospective Cross-Sectional Study Using the Repeatable Battery for the Assessment of Neuropsychological Status Adjusted for the Hearing Impaired in the DFNA9 Population. Ear and hearing 10 36607747
2021 COCH predicts survival and adjuvant TACE response in patients with HCC. Oncology letters 9 33732351
2020 Homozygote loss-of-function variants in the human COCH gene underlie hearing loss. European journal of human genetics : EJHG 9 32939038
2020 Correlations Between Vestibular Function and Imaging of the Semicircular Canals in DFNA9 Patients. Frontiers in neurology 8 31998212
2011 Phenotype analysis of an Australian DFNA9 family with the 1109N COCH mutation. The Annals of otology, rhinology, and laryngology 8 21774451
2015 A novel frameshift variant of COCH supports the hypothesis that haploinsufficiency is not a cause of autosomal dominant nonsyndromic deafness 9. Biochemical and biophysical research communications 7 26631968
2010 Extralabyrinthine manifestations of DFNA9. Journal of the Association for Research in Otolaryngology : JARO 7 21052762
2007 Vertical corneal striae in families with autosomal dominant hearing loss: DFNA9/COCH. American journal of ophthalmology 7 17368553
2017 Different Phenotypes of the Two Chinese Probands with the Same c.889G>A (p.C162Y) Mutation in COCH Gene Verify Different Mechanisms Underlying Autosomal Dominant Nonsyndromic Deafness 9. PloS one 6 28099493
2005 [From gene to disease; a progressive cochlear-vestibular dysfunction with onset in middle-age (DFNA9)]. Nederlands tijdschrift voor geneeskunde 6 16355574
2013 Analysis of COCH and TNFA variants in East Indian primary open-angle glaucoma patients. BioMed research international 5 24063017
2023 Rational design of a genomically humanized mouse model for dominantly inherited hearing loss, DFNA9. Hearing research 4 38218018
2025 Self-supported Fe,Mn-CoCH/NF electrocatalyst for oxygen evolution reaction. Journal of colloid and interface science 3 41046611
2024 Interaural and sex differences in the natural evolution of hearing levels in pre-symptomatic and symptomatic carriers of the p.Pro51Ser variant in the COCH gene. Scientific reports 3 38167558
2022 Involvement of cochlin binding to sulfated heparan sulfate/heparin in the pathophysiology of autosomal dominant late-onset hearing loss (DFNA9). PloS one 3 35901072
2016 Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH. Neural plasticity 3 28116169
2025 Cochlear health in a cohort of cochlear implant users carrying the p.Pro51Ser variant in the COCH gene (DFNA9): A cross-sectional study evaluating the changes in the electrically evoked compound action potential (eCAP). Hearing research 2 40088601
2023 Evaluation of hearing levels and vestibular function and the impact on cognitive performance in (pre)-symptomatic patients with DFNA9: protocol for a prospective longitudinal study (Rosetta study). BMJ open 2 37709329
2021 A Novel COCH Mutation Affects the vWFA2 Domain and Leads to a Relatively Mild DFNA9 Phenotype. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 2 33710989
2019 First Report of Bilateral External Auditory Canal Cochlin Aggregates ("Cochlinomas") with Multifocal Amyloid-Like Deposits, Associated with Sensorineural Hearing Loss and a Novel Genetic Variant in COCH Encoding Cochlin. Head and neck pathology 2 31493294
2016 Sequencing of exons 4, 5, 12 of COCH gene in patients with postlingual sensorineural hearing loss accompanied by vestibular lesion. Archives of medical science : AMS 2 29765451
2005 RT-PCR analysis of Tecta, Coch, Eya4 and Strc in mouse cochlear explants. Neuroreport 2 15729138
2025 Nonequilibrium Synthesis of Glycolamide (NH2COCH2OH), a Precursor to Amino Acids, on Interstellar Nanoparticles. ACS central science 1 41907502
2022 Does Vestibulo-Ocular Reflex (VOR) Gain Correlate With Radiological Findings in the Semi-Circular Canals in Patients Carrying the p.Pro51Ser (P51S) COCH Variant Causing DFNA9? Relationship Between the Three-Dimensional Video Head Impulse Test (vHIT) and MR/CT Imaging. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 1 35020687
2010 Molecular cloning of the Coch gene of guinea pig inner ear and its expression analysis in cultured fibrocytes of the spiral ligament. Acta oto-laryngologica 1 20629486
2007 [Mutation screening of the COCH gene in familial and sporadic patients with late onset nonsyndromic sensorineural hearing loss among Chinese population]. Zhonghua yi xue za zhi 1 18269866
2026 Catalysis of Acetone Enolization by Nitrogen-Containing Ligands: An Infrared Spectroscopic Study of (CH3COCH3-X)+ Complexes (X = CH3CN, CH2CHCN, NH3). The journal of physical chemistry. A 0 41528991
2026 Performance Results and Timing of Cochlear Implantation in Patients With DFNA9 (p.Pro51Ser). Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 0 42259506
2025 Early Deficits in Speech Perception in Carriers of the p.Pro51Ser Variant in the <italic>COCH</italic> Gene: A Prospective Longitudinal Evaluation of Speech Perception in Quiet and Noise. Audiology & neuro-otology 0 39864432
2024 Hearing and Vestibular Impairment Related to a Variant (c.263G>C) of the COCH Gene. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 0 39666779
2021 Predictive Sensitivity and Concordance of Machine-learning Tools for Diagnosing DFNA9 in a Large Series of p.Pro51Ser Variant Carriers in the COCH-gene. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 0 33492061
2015 [Phenotype predictions of the pathogenic nonsynonymous single nucleotide polymorphisms in deafness-causing gene COCH]. Yi chuan = Hereditas 0 26351166
2012 [Genotype--phenotype correlation limits in sensorineural hearing loss: case report of a three-year-old child with a bilateral cochleovestibular impairment and a molecular variant of the COCH gene]. Revue de laryngologie - otologie - rhinologie 0 23590105

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